Tuberculosis and targeted synthetic or biologic DMARDs, beyond tumor necrosis factor inhibitors

Abstract

Patients with autoimmune rheumatic diseases (ARD) have an increased risk for tuberculosis (TB). The use of tumor necrosis factor inhibitors (TNFi) and glucocorticoids in these patients has been associated with an increased prevalence of latent TB reactivation. Over the last few years, several biologic disease-modifying anti-rheumatic drugs (bDMARDs), other than TNFi (e.g. rituximab, abatacept, tocilizumab, secukinumab) and targeted synthetic DMARDs (tsDMARDs) [e.g. apremilast, Janus kinase (JAK) inhibitors] have been used for the treatment of patients with ARD. For many of these drugs, especially the newer ones like JAK inhibitors or antibodies against interleukin (IL)-23, most data stem from randomized clinical trials and few are available from real life clinical experience. We sought to review the current evidence for TB risk in patients with ARD treated with tsDMARDs or bDMARDs, other than TNFi. It seems that some of these drugs are associated with a lower TB risk, indirectly compared with TNFi treatment. In fact, it appears that rituximab, apremilast and inhibitors of IL-17 and IL-23 might be safer, while more data are needed for JAK inhibitors. As seen in TNFi, risk for TB is more pronounced in TB-endemic areas. Screening for latent TB must precede initiation of any tsDMARDs or bDMARDs. The growing use of non-TNFi agents has raised the need for more real-life studies that would compare the risk for TB between TNFi and other treatment modalities for ARD. Knowledge about the TB-safety profile of these drugs could help in the decision of drug choice in patients with confirmed latent TB infection or in TB endemic areas.

Use of IL-23 Inhibitors for the Treatment of Plaque Psoriasis and Psoriatic Arthritis: A Comprehensive Review

“…Given the novelty of these drugs, long-term studies to carefully monitor for the development of more serious side effects are naturally required. Of note is the risk of serious infection and reactivation of diseases such as TB in light of immune system modulation, as seen in TNF-α inhibitors [97]. However, IL-23 inhibitors were not shown to increase the risk for TB infection or reactivation.…”

Prednisone reduction for metastatic castration-resistant prostate cancer with recurrent pulmonary tuberculosis

“…Besides, the granuloma is the long-term survival nest of some tuberculosis bacilli in the body, which is the infection stage of latent tuberculosis, and any factor leading to immunosuppression may destroy the delicate balance of latent tuberculosis and cause tuberculosis infection to reactivate. [ 15 ] The functions of glucocorticoids include but are not limited to: antagonize macrophages, inhibit macrophages to produce interleukin-1, interleukin-6, tumor necrosis factor, pro-inflammatory prostaglandins, leukotrienes, and inhibit the activity of activated antitumor and microbial macrophages, moreover, if the dosage of prednisone is increased by 1 g, the risk of tuberculosis will be increased by 23%. [ 16 ]…”

Infectious Complications in Autoimmune Hemolytic Anemia

“…B cells appear to play a minor role in controlling TB infection [ 92 ]. Consistently, rituximab has not been associated with TB reactivation in patients with RA, Sjogren’s syndrome, SLE, mixed cryoglobulinemia, and vasculitides [ 88 ]. In AIHA, the risk of TB reactivation seems low, although attention should be paid to high and/or prolonged steroids use.…”

“…Host responses against Mycobacterium tuberculosis are mediated by a delicate interplay between innate and adaptive immunity, dominated by macrophages and T cells, respectively. An alteration of these regulatory mechanisms may result in active TB infection/reactivation [ 88 ]. In RA, glucocorticoids and methotrexate are associated with a slightly increased risk of TB infection, whilst tumor necrosis factor (TNF)-inhibitors carry a 4- to 8-fold risk [ 89 ].…”